Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system resulting from loss of immune tolerance. Many disease-modifying therapies for MS have broad immunosuppressive effects on peripheral immune cells, but this can increase risks of infection and attenuate vaccine-elicited immunity. A more targeted approach is to re-establish immune tolerance in an autoantigen-specific manner. This review discusses methods to achieve this, focusing on tolerogenic dendritic cells. Clinical trials in other autoimmune diseases also provide learnings with regards to clinical translation of this approach, including identification of autoantigen(s), selection of appropriate patients and administration route and frequency.
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http://dx.doi.org/10.1016/j.jneuroim.2024.578347 | DOI Listing |
Acta Biomater
January 2025
Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan. Electronic address:
Tolerogenic dendritic cells with professional antigen presentation via major histocompatibility complex molecules, co-stimulatory molecules (CD80/86), and interleukin 10 production have attracted significant attention as cellular therapies for autoimmune, allergic, and graft-versus-host diseases. In this study, we developed a cell culture dish equipped with polycation-porphyrin-conjugate-immobilized glass (PA-HP-G) to stimulate immature murine dendritic cell (iDCs). Upon irradiation with a red light at 635 nm toward the PA-HP-G surface, singlet oxygen was generated by the immobilized porphyrins on the PA-HP-G surface.
View Article and Find Full Text PDFFront Immunol
January 2025
Amgen Research, Amgen Inc., South San Francisco, CA, United States.
J Allergy Clin Immunol
January 2025
National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address:
Background: Peanut allergy (PA) is one of the most prevalent food allergies with a lack of favorable safety/efficacy treatment. A cucumber mosaic virus-like particle expressing peanut allergen component Ara h 2 (VLP Peanut) has been developed as a novel therapeutic approach for PA.
Objective: We assessed the tolerogenic properties and reactivity of VLP Peanut.
Clin Transl Med
December 2024
Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucía-University of Pablo de Olavide-University of Seville-CSIC, Seville, Spain.
Background: The complex aetiology of type 1 diabetes (T1D), characterised by a detrimental cross-talk between the immune system and insulin-producing beta cells, has hindered the development of effective disease-modifying therapies. The discovery that the pharmacological activation of LRH-1/NR5A2 can reverse hyperglycaemia in mouse models of T1D by attenuating the autoimmune attack coupled to beta cell survival/regeneration prompted us to investigate whether immune tolerisation could be translated to individuals with T1D by LRH-1/NR5A2 activation and improve islet survival.
Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from individuals with and without T1D and derived into various immune cells, including macrophages and dendritic cells.
Background: Allergen-specific immunotherapy (AIT) is so far the only disease-modifying therapy for allergy, resulting in a long-lasting tolerance. However, the existing safety concerns and the need for more efficacious alternatives that shorten the duration of treatment have stimulated research into the development of novel alternatives. Some of these novel alternatives involve modifying allergens with molecules that target innate immunomodulatory receptors to suppress the immune activity of immune cells.
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